What Protective Effect Of Α -lipoic Acid ( La ) Against Oxidative Stress And Apoptosis

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

Patient P has a limited medication history, however, other factors are detrimental to control in order to prevent negative effects on the oral cavity and the overall health of the body. The factors of concern for Patient P include tobacco use, alcohol intake, prehypertension, plaque biofilm, and calculus formation. Patient P is currently taking mucinex due to seasonal allergies. Mucinex can also cause oral side effects that can impact treatment. Tobacco use and alcohol intake is a major concern in order to prevent health risks to the oral cavity and to the overall body.

Half of the animals will be euthanized on day 28 (before the second DSS cycle), and the other half on day 56. This will allow us to study ROS production and DNA stability before the onset of neoplasia (28 days), and once it is established (56 days). We have an extensive experience in this animal model6,8,10. Power calculations indicate we will need an n=8 mice per group to obtain significant results31. Colon will be processed for histology and epithelial cell isolation by chelation in EDTA. Part of these epithelial cells will be kept for RNA isolation, part will be used for ROS determination, and the rest will be seeded in extracellular matrices to grow them as organoids. Organoids will be cultured for 7 days to allow for additional divisions in the presence or absence of 1µg/mL LPS32. Epithelial cells in tissues and culture will be analyzed for DNA damage and genetic instability via γH2AX immunofluorescence (a marker for DNA damage), presence of anaphase bridges, and telomere staining. Dr. Verdun´s lab is very experienced in these techniques33,34. Epithelial cells will be interrogated for the expression of Duox2, SOD1, CAT, GPX2, and GPX4 (quantitative PCR) as markers of oxidative stress in epithelial cells35, and production of ROS will be measured by staining with DCFDA and Amplex Red probes. These experiments will indicate to which extent DNA damage induced by ROS is mediated by TLR4 activation in the

Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological

Emerging evidence indicates that free radicals are involved in the pathogenesis of several digestive system disorders as well as in the regulation of biological processes such as aging. Previous reports have indicated that opioids induce apoptosis via stimulating an oxidative stress pathway that is associated with the production of superoxide and nitric oxide (NO) [11]. NO, together with reactive oxygen species (ROS), has a pivotal role in the regulation of apoptosis and necrosis in various cells. Hsiao et al. investigated the role of NO and ROS in the morphine-induced apoptosis. They found that the morphine treatment enhanced apoptosis through both NO and ROS pathways [12]. The inducible nitric oxide synthase (iNOS) enzyme is one of the most important enzymes involved in the generation of NO from the amino acid L-arginine.

Urate hydroperoxide inactivated GAPDH in a dose-dependent manner. The ratio of urate hydroperoxide to inactivated GAPDH was ~6:1. When I reduced GAPDH with DTT I recovered half of the activity. In comparison, taurine chloramine inactivated GAPDH at ratio ~10:1 and all the activity was recovered with DTT. My results suggest urate hydroperoxide permanently inactivates GAPDH. Future work will investigate urate hydroperoxide inactivation of other thiol-dependent enzymes. My research furthers our understanding of the pro-oxidant effects of urate. Urate hydroperoxide links hyperuricemia, oxidative stress and inflammatory

Some treatments for other diseases such as cancer, may negatively affect the gums making them more susceptible to gum disease.

Jones, A. E. & H., G., 1963. Oxidation of succinate and the control of the citric acid cycle in the mitochondria of guinea-pig liver, mammary gland and kidney. Biochemical Journal, 87(3), p. 639–648.

other rapidly growing cells in the body. Chemotherapeutic drugs used to treat cancer are given to most of the people, which help to sustain the completion of cancer treatment (El-Sayyad et al., 2009; Sundaram & Sangavai, 2009). Besides this, the noxious side effects of chemotherapeutic agents include the devastating production of reactive oxygen species (ROS). Therefore, an escalating amount of facts suggest that a simultaneous treatment of chemotherapy and chemo-preventive agents with antioxidant action may augment the efficacy of chemotherapeutics (Lee et al., 2008;Aydin et al., 2011). Although the mechanism underlying the severe cytotoxicities of doxorubicin (DOX) is not fully clear, ROS are assumed to be a key factor in the toxicity of DOX and events controlling this oxidative injury are extensively appreciated (Reddy

Martin SG, Michael G, Jonsthsn A. (2008). Burket’s oral Medicine.11th ed. Ontario.BC Decker Inc. E-book.

Although all in vitro models have limitations, our studies described in this thesis have demonstrated that these models, when used appropriately, will enable us to investigate specific research questions under different circumstances. By using different human-based in vitro models, our current findings have indicated that the high-dose APAP induces mitochondrial dysfunction, including the decrease in ATP synthesis and the increase in mitochondrial ROS formation, by disrupting the expression of key genes encoding the elements of respiratory chain complexes and mitochondrial and cellular specific antioxidants in both normal and inflamed livers (Chapter III and Chapter V). Besides, the whole-genome expression data obtained from PHH have suggested the high interindividual variation in the expression of genes participating in the Phase I/III drug metabolism/transport at baseline and the APAP-induced variation in genes involved in immune response may influence susceptibility to APAP hepatotoxicity (Chapter IV). The exposure of a 3D co-culture model to APAP with/without LPS has revealed the interaction between PHH and KCs (Chapter V). Through this novel model, we have identified that the median-dose APAP may reduce the KC phagocytic capacity by inhibiting the expression of Fcγ receptor-coding genes and prolong the clearance of pathogen and cell debris, which enhance KC mediated inflammatory response and exacerbate liver damage in

Apart from lycopene, serum level of Ascorbic acid, alpha Tocopherol result consistent. The measurement of depletion is alpha Tocopherol = Retinol which effect on redox and immune system in both active and passive smokers. Lifestyle remodeling is compulsive for smokers with specific modulator because of the direct exposure on human plasma engender serious pulmonary abrasions. The direct exposure to hydrocarbon gas phase decline 80% of lycopene concentration by the formation of buccal mucosal cells. (69) In order to upgrade the biological activities at synergistic effect on homogenized samples with atherosclerotic plaques of (0.04 ± 0 .065mmol/mol) require contents of human carotid and iliac arteries at medicine and analytic chemistry. Further clarifications of retinoid are needed to be directive mainly at unstable impairment of conversions.(70) The correlated value of serum reflect biomarkers AST, ALT, Bilirubin, Triglyceride, oxaloacetic transaminase with 20-25 folds shorter leading to Alcoholic cirrhosis and Hepatic

Today's medical physicians and oral physicians are taking a more holistic look at diseases of the human body and their origins: prolonged stress, poor diet, lack of spirituality and lack of exercise. However, a link was missing where oral health was concerned. Today, the connection of illnesses originating from the mouth and spreading to the rest of the body becomes all the more apparent with each passing

Mitochondria are a major source of cell superoxide generation that in turn yields a spectrum of secondary reactive species. They serve multiple functions, including regulation of intracellular calcium stores, ATP production, activation of caspases, and regulation of redox signaling. The outer mitochondrial membrane is porous and allows for passage of low molecular substances between the cytosol, the inter-mitochondrial compartment, and the matrix. Mitochondrial dysfunction is characterized by a decreased ATP production, decreased membrane potential, decreased expression of mitochondrial complexes I, III, IV and increased mitochondrial respiration and ROS production, has been observed in the inflamed airways of asthmatic subjects. Excessive

3A). However, other nucleotides like deoxycytidine (Fig. 3A) are glycated at high α-oxoaldehyde concentrations forming 5-glycolylcytidine (Frischmann, M. et al 2005; Kasai, H. et al 1998; Krymkiewicz, N. 1993). Inter-strand cross-links in duplex DNA (Seidel W and Pischetsrieder M 1998; Kasai, H. et al 1998) and DNA–protein cross-links in human keratinocytes were reported at higher MG concentrations. A recent in vitro study has demonstrated that CEdG (Fig. 3B) formation in DNA can hinder the Klenow fragment-mediated DNA synthesis (Cao, H. et al 2007). Due to AGEs the hydrogen-bonding property of the modified guanine is affected, resulting efficient incorporation of purine than pyrimidine nucleotides (Cao, H. et al 2007). Addition of bulky AGEs groups on the N2 position of guanine altered the Watson–Crick base pairing characteristic of these nucleobases resulting in destabilization of duplex DNA. The presence of dGTP-AGEs in DNA may change DNA structure, leading to the formation of abasic sites and DNA strand breaks (Pischetsrieder, M. et al 1999; Seidel W and Pischetsrieder M 1998; Cao, H. et al 2007). DNA glycation generates several nucleotide adducts that increases oxidative stress by the generation of hydrogen peroxide, superoxide, and hydroxyl radicals (Mistry, M. et al 2003; Thornalley, P.J. 1996). Recently a study demonstrated an accumulation of